Pitt Pediatrics congratulates Robert Nicholls, DPhil and colleagues, including first author Erik Koppes, PhD, for their recent publication in PLOS Genetics, “Insulin secretion deficits in a Prader-Willi syndrome β-cell model are associated with a concerted downregulation of multiple endoplasmic reticulum chaperones.” Nicholls, a Professor of Pediatrics in the Division of Genetic and Genomic Medicine, is a career-long expert in Prader-Willi syndrome (PWS), and has earned a lifetime achievement award for his ongoing research from the Prader-Willi Syndrome Association (PWSA) in 2013. 
PWS is generally characterized as a multisystem genetic disorder that can have effects on hormonal, metabolic, and neurobehavioral characteristics in pediatric and adult patients. Previous research models on PWS have suggested an imbalance of insulin retention and secretion in the pancreas. Nicholls, and other involved authors of this study, in order to determine the role of PWS in beta-cell biology, designed a procedure using genome-editing to generate PWS beta-cells. Results indicated that PWS beta-cell lines did have a significant impact on levels of secretion for insulin and other hormones.
This complicated genetic relationship suggests that a chronic shortage of a specific type of protein chaperones (which allow secreted proteins to traffic properly) may ultimately result in a deficiency in protein folding, or delay in other necessary functionality. Ultimately, the research provides a mechanistic understanding of a source of PWS symptoms, especially for hormone deficits in PWS patients. The work also identifies new pathways critical for insulin release in the function of beta-cells, a process defective in diabetes.
Follow Pitt Pediatrics on Twitter and the research pages on the Genetics Division website for ongoing updates on Nicholls’ research.